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Atorvastatin ameliorates cerebral vasospasm and early brain injury after subarachnoid hemorrhage and inhibits caspase-dependent apoptosis pathway.

Cheng G, Wei L, Zhi-Dan S, Shi-Guang Z, Xiang-Zhen L - BMC Neurosci (2009)

Bottom Line: Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH.TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin.The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, PR China. doctorgaocheng@yahoo.com.cn

ABSTRACT

Background: Cerebral vasospasm (CVS) and early brain injury remain major causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH. This study was designed to explore apoptosis inhibiting effects of atorvastatin and its potential apoptotic signal pathway after SAH.

Results: Preserving blood-brain-barrier permeability, decreasing brain edema, increasing neurological scores and ameliorating cerebral vasospasm were obtained after prophylactic use of atorvastatin. TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin. Apoptosis-related proteins P53, AIF and Cytochrome C were up-regulated after SAH, while they were not affected by atorvastatin. In addition, up-regulation of caspase-3 and caspase-8 after SAH was decreased by atorvastatin treatment both in mRNA and in protein levels.

Conclusion: The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.

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Related in: MedlinePlus

Western blot for expression of caspase-3 and caspase-8. Obvious increase of caspase-3 (P17) and caspase-8 (P18) was obtained in basal cortex, which was attenuated by atorvastatin. A, Represent expression of caspase-3. B, Represent expression of caspase-8. C, Each column represents 5 independent experimental results. (1, Sham operated control; 2, SAH; 3, SAH + Atorvastatin; 4, SAH+DMSO *, P < 0.05 vs DMSO group).
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Figure 3: Western blot for expression of caspase-3 and caspase-8. Obvious increase of caspase-3 (P17) and caspase-8 (P18) was obtained in basal cortex, which was attenuated by atorvastatin. A, Represent expression of caspase-3. B, Represent expression of caspase-8. C, Each column represents 5 independent experimental results. (1, Sham operated control; 2, SAH; 3, SAH + Atorvastatin; 4, SAH+DMSO *, P < 0.05 vs DMSO group).

Mentions: Apoptosis-related proteins were examined in hippocampus and basal cortex. Elevated level of cleaved caspase-3, caspase-8, AIF, P53 and Cytochrome C were observed in SAH group (P < 0.05 versus sham operated control group). While no significant difference was found of bax and bcl-2 proteins levels between SAH and sham operated control rats. Atorvastatin reduced the expression of cleaved caspase-3 and caspase-8 (P < 0.05 versus vehicle treated rats), but had no obvious influence on expression of AIF, P53 and Cytochrome C. Atorvastatin had no statistical effects on both bax and bcl-2 at 24 hour after SAH (Figure 3, 4, 5).


Atorvastatin ameliorates cerebral vasospasm and early brain injury after subarachnoid hemorrhage and inhibits caspase-dependent apoptosis pathway.

Cheng G, Wei L, Zhi-Dan S, Shi-Guang Z, Xiang-Zhen L - BMC Neurosci (2009)

Western blot for expression of caspase-3 and caspase-8. Obvious increase of caspase-3 (P17) and caspase-8 (P18) was obtained in basal cortex, which was attenuated by atorvastatin. A, Represent expression of caspase-3. B, Represent expression of caspase-8. C, Each column represents 5 independent experimental results. (1, Sham operated control; 2, SAH; 3, SAH + Atorvastatin; 4, SAH+DMSO *, P < 0.05 vs DMSO group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651177&req=5

Figure 3: Western blot for expression of caspase-3 and caspase-8. Obvious increase of caspase-3 (P17) and caspase-8 (P18) was obtained in basal cortex, which was attenuated by atorvastatin. A, Represent expression of caspase-3. B, Represent expression of caspase-8. C, Each column represents 5 independent experimental results. (1, Sham operated control; 2, SAH; 3, SAH + Atorvastatin; 4, SAH+DMSO *, P < 0.05 vs DMSO group).
Mentions: Apoptosis-related proteins were examined in hippocampus and basal cortex. Elevated level of cleaved caspase-3, caspase-8, AIF, P53 and Cytochrome C were observed in SAH group (P < 0.05 versus sham operated control group). While no significant difference was found of bax and bcl-2 proteins levels between SAH and sham operated control rats. Atorvastatin reduced the expression of cleaved caspase-3 and caspase-8 (P < 0.05 versus vehicle treated rats), but had no obvious influence on expression of AIF, P53 and Cytochrome C. Atorvastatin had no statistical effects on both bax and bcl-2 at 24 hour after SAH (Figure 3, 4, 5).

Bottom Line: Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH.TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin.The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, PR China. doctorgaocheng@yahoo.com.cn

ABSTRACT

Background: Cerebral vasospasm (CVS) and early brain injury remain major causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH. This study was designed to explore apoptosis inhibiting effects of atorvastatin and its potential apoptotic signal pathway after SAH.

Results: Preserving blood-brain-barrier permeability, decreasing brain edema, increasing neurological scores and ameliorating cerebral vasospasm were obtained after prophylactic use of atorvastatin. TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin. Apoptosis-related proteins P53, AIF and Cytochrome C were up-regulated after SAH, while they were not affected by atorvastatin. In addition, up-regulation of caspase-3 and caspase-8 after SAH was decreased by atorvastatin treatment both in mRNA and in protein levels.

Conclusion: The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.

Show MeSH
Related in: MedlinePlus